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Injectable PrEP Frequently Asked Questions – Clinical

The information in this FAQ provides general guidance and reflects what is currently understood about Cabotegravir-LA (Apretude) based on data from HPTN 083 and post-marketing experience. Readers should consult the package insert and/or obtain expert guidance in the management of individual patients.
1. What is the time to protection of CAB-LA for injectable PrEP?
  • Time to protection is not known with certainty for any form of PrEP.
  • The available evidence based on animal models suggests 95% of people will achieve protective blood levels of CAB-LA 7 days after their first injection. Fifty percent of people will achieve protective blood levels 1 day after the first injection.

See detailed information in Appendix 1: “Time to onset of protection with Long-Acting Cabotegravir when used as Pre-exposure Prophylaxis”

Additional information

For reference, the target blood level is 0.664 μg/mL, which is four times the protein-adjusted (PA)-IC90. The IC90 of a drug is the drug concentration that will inhibit replication of 90% of HIV virus. The plasma concentrations associated with protection were identified in preclinical animal and phase 2 trials. In animal studies, >1X PA IC90 was 97% protective for nonhuman primates, and >3X PA IC90 was 100% protective. In phase 2 trials, 600mg of CAB LA dosed every 8 weeks resulted in plasma concentrations >4X PA IC90 for the majority of the population studied. This dose was moved forward for the HPTN studies. Four times that level is thought to be a conservative enhancement of that level of viral inhibition.

2. Is an oral PrEP lead-in recommended before a patient receives the first CAB-LA injection?
  • Given the delay many patients will experience obtaining CAB-LA, clinicians should consider a rapid initiation of oral PrEP for any patient requesting such protection – to delay PrEP initiation in these circumstances exposes patients to ongoing risk of HIV acquisition.
  • If patients or providers have concerns about tolerability of CAB-LA, an oral lead-in with oral cabotegravir is a reasonable option.
  • Clinically, a lead in of oral cabotegravir is not needed to achieve adequate blood levels of CAB-LA upon initiation of injections.

Additional information

In HIV-1 treatment clinical trials, data demonstrated that an oral lead-in is not needed to ensure adequate plasma cabotegravir exposure upon initiation of injections and that the safety and efficacy results of cabotegravir extended-release injectable suspension plus rilpivirine extended-release injectable suspension were similar when administered with and without an oral lead-in. There were no discontinuations of oral cabotegravir among almost 4,000 participants in HPTN 083/084 due to drug-related hypersensitivity, supporting the optional status of the oral lead-in on the package inset. It may be a reasonable option for patients and providers with concerns about tolerability; but patient and provider concern about the adherence burden of a daily oral pill might also be considered.

3. Can oral cabotegravir be used for oral PrEP prior to the first injection of CAB-LA?
  • Oral cabotegravir tablets for this purpose – that is, explicitly as an HIV prevention strategy– is technically “off-label” according to the FDA package insert.
  • FDA approved regimens to date for oral PrEP include generic TDF-FTC, or brand Truvada (TDF-FTC ) or Descovy (TAF-FTC)

See Appendix 2: Apretude package insert

Additional information

Oral cabotegravir tablets were approved for assessing tolerance to this drug compound and for short-term PrEP in the setting of planned missed doses (see below).

4. Under what circumstances is oral cabotegravir approved for PrEP?
  • To cover known delays or gaps in CAB-LA of up to two months, when the patient plans to miss an injection visit but wishes to continue CAB-LA as soon as interrupting factors are resolved.

See Appendix #3 ”Continuing CAB-LA following Planned or Unplanned Missed Injections” for recommendations

5. What if a patient wants to take the cabotegravir oral lead in for only one week, and then switch to the injectable form?
  • The decision to administer a shorter course of oral cabotegravir lead-in (<28 days) to assess medication tolerability is up to the provider, in consultation with the patient.

Additional information

The oral cabotegravir lead-in is optional and in the HPTN studies, it was administered for 5 weeks.

6. If a patient has been maintained on injectable CAB-LA for, say, 4-6 months, but then needs to be transitioned back permanently to oral PrEP what is the best strategy?
  • It would be reasonable to restart daily oral PrEP (TAF-FTC or TDF-FTC) 7 days prior to the date on which the next CAB-LA injection would have been administered, were the patient to have continued injectable PrEP.
7. For patients who want to stop CAB-LA injections but have ongoing risk for HIV infection, by when should they start taking oral PrEP?
  • An alternative form of PrEP should be initiated within 2 months of the final CAB-LA injection. Ideally, 7 days prior to the date on which the next CAB-LA injection would have been administered.

See Appendix 2: Apretude package insert

8. How soon can a patient stop taking FDA approved oral PrEP regimens once they have received the 1st starter dose of CAB-LA?
  • Available evidence suggests that seven days after the first CAB-LA injection would be the appropriate time to stop oral TDF-FTC or TAF-FTC.

Additional information

Based on population PK modeling, 95% of the population would have CAB LA levels consistent with protection within 7 days following the initial injection. In the ongoing open label extensions, participants are being switched without overlap; data on switch from oral TDF/FTC to CAB LA are being collected.

9. What is meant by the CAB-LA “tail” and what risk does it relay to patients?
  • There is a theoretical risk that if a CAB-LA patient is lost to follow-up, and experiences a very gradual waning of CAB-LA drug levels over many months (up to a year perhaps), not only is the patient at risk of acquiring HIV, but were the patient to contract HIV infection in this time period, the exposure to subtherapeutic blood levels of CAB-LA could induce drug resistance in the acquired virus – resistance to either cabotegravir, or perhaps the entire integrase inhibitor class of antiretrovirals more broadly.

Additional information

Fortunately, in study results available to date, HIV seroconversions have not been documented. However, numbers observed to date have been relatively small, so caution is recommended in drawing definitive conclusions especially in patient communications.

10. Are there any gender differences of clinical or practical concern in the use of CAB-LA for HIV PrEP?
  • According to available data, there are no gender differences in clinical or practical concerns in the use of CAB-LA for HIV PrEP. Therefore, neither counseling messages nor prescribing practices need to be varied based on the gender of the patient/client, or whether the patient/client is at risk of HIV infection due to vaginal versus anal sex/exposure, etc.

Additional information

Of note, aside from plasma levels of CAB-LA, there was no sampling of anatomic tissue compartments in HPTN 083 or 084 to predict with certainty what drug levels would be in those compartments. However, there were no observed differences between participants of different genders in the studies.

11. Are there any known drug-drug interactions between currently available oral PrEP medications and CAB-LA?
  • No.
12. Are there any concerns about CAB-LA and gender affirming hormone therapy (GAHT)?
  • Not according to available data.

Additional information

According to available data, there are no differences in clinical or practical concerns in the use of CAB-LA for HIV PrEP for persons on hormone therapy. Transgender women were included in HPTN 083 The cabotegravir-LA label does not call for any dose adjustments for persons on GAHT.

13. Are there any data on CAB-LA efficacy and BMI?
  • No, there are no data to support varying dosage amount or frequency based on weight or BMI.
  • A longer needle length should be considered for persons who weigh >30 kg to ensure the medication reaches the gluteus muscle.

For additional clinical support, contact the National Clinician Consultation Center PrEP line:

(855) 448-7737 or (855) HIV-PrEP, Monday – Friday, 9 am – 8 pm ET.